Summary of Gain Therapeutics Conference Call Company Overview - **Company**: Gain Therapeutics (NasdaqGM:GANX) - **Focus**: Development of GT02287 for Parkinson's disease treatment Key Industry Insights - **Parkinson's Disease Prevalence**: Second most prevalent neurodegenerative disease in the U.S. with approximately 1 million patients, 15% of whom carry a GBA1 mutation [8][2] - **GCase Activity**: The enzyme glucocerebrosidase (GCase) is crucial in the pathophysiology of Parkinson's, with mutations leading to reduced enzyme activity and associated disease progression [12][18] Core Findings from the Conference Call - **Phase 1b Study Results**: - Patients showed an average improvement of 2.2 points in MDS-UPDRS scores after 90 days of treatment with GT02287 [2][10] - The improvement aligns with expectations based on the drug's mechanism of action [3] - A clinically meaningful improvement is considered to be approximately six points over a year compared to placebo [3] - **Biomarker Evidence**: - GT02287 modulates GCase activity, leading to a reduction in glucosylsphingosine, a toxic substrate implicated in Parkinson's [4][5] - Stabilization of MDS-UPDRS scores observed without changes in dopamine administration suggests a potential disease-modifying effect [5][42] - **Study Design**: - The phase 1b study included a 90-day treatment followed by an optional open-label extension [8][26] - 21 patients enrolled, with 19 completing the first part of the study [26] - **Future Expectations**: - Continued analysis of phase 1b study extension and safety [42] - Final results expected in the second half of 2026, with plans to initiate a phase II study [43][44] Important Considerations - **Glucosylsphingosine as a Biomarker**: - Emerging evidence suggests glucosylsphingosine is a better biomarker for treatment response than glucosylceramide [35][36] - Measurement in cerebrospinal fluid (CSF) is critical for assessing central nervous system effects [36] - **Regulatory Pathway**: - Discussions with the FDA regarding the use of glucosylsphingosine as a surrogate biomarker are ongoing, but traditional UPDRS-based studies may still be required for approval [55][56] - **Patient Population**: - Future studies may focus on patients with specific glucosylsphingosine levels or GBA1 mutations, as they may respond better to treatment [46][49] Additional Insights - **Mechanism of Action**: - The drug aims to increase GCase activity, potentially leading to reduced glucosylsphingosine levels, which could have long-term benefits for Parkinson's patients [34][38] - **Clinical Implications**: - The reduction of glucosylsphingosine in CSF correlates with improvements in UPDRS scores, indicating a possible link between biomarker levels and clinical outcomes [41][45] This summary encapsulates the key points discussed during the conference call, highlighting the company's focus on GT02287, the significance of biomarker evidence, and the implications for future clinical development and regulatory interactions.

申可安 的成功获批是齐鲁制药在中枢神经治疗领域的一项重要进展。作为中国大型综合性现代制药企 业，齐鲁制药建有包括"药物制剂国家工程研究中心"在内的多个国家级研发平台。产品治疗覆盖肿瘤、 感染、心脑血管、精神神经系统、眼科、自身免疫、糖尿病等多个领域。 阿里健康作为"新特药首发阵地"，此次作为申可安 的首发渠道，为其提供了快速触达目标患者的路 径，并依托专业的医学科普、药师服务与便捷的购药配送网络，助力帕金森病患者获得更可及的疾病管 理方案。 我国是帕金森病大国。随着病程进展，长期接受左旋多巴治疗的患者中，相当一部分会出现"剂末现 象"，即药效持续时间缩短，在下次服药前运动症状反复加重，影响日常生活能力与生活质量。 申可安 通过将左旋多巴、卡比多巴与恩他卡朋三种成分整合为单一复方片剂。在《中国帕金森病治疗 指南》中，推荐该类复方左旋多巴制剂作为出现运动波动患者的首选治疗方案，而恩他卡朋和卡比多巴 可提高左旋多巴入脑水平，延长其半衰期，同时减少多巴胺在外周的生成，进而有效减轻外周不良反 应。此外，将三种成分制成一片，也简化了用药方案，有助于提升患者长期治疗的依从性。 12月22日，齐鲁制药集团有限公司旗下恩他卡朋 ...

Core Viewpoint - The approval of the controlled-release formulation of Carbidopa-Levodopa by the National Medical Products Administration enhances the company's product pipeline in the Parkinson's disease treatment sector, particularly with the introduction of a first generic version in the domestic market [1] Group 1: Product Approval - The company received two drug registration certificates for Carbidopa-Levodopa controlled-release tablets [1] - The specifications for the approved products include Carbidopa 50mg and Levodopa 200mg, and Carbidopa 25mg and Levodopa 100mg [1] - The latter specification is the first generic version in China, as the original product has not been registered for sale domestically [1] Group 2: Market Impact - The approval enriches the company's offerings in the Parkinson's disease treatment market, providing a significant opportunity in a niche segment [1] - The controlled-release formulation is recognized as the "gold standard" for treating Parkinson's disease according to the "Chinese Parkinson's Disease Treatment Guidelines (2020 Edition)" [1] - The availability of the smaller dosage form improves medication convenience for patients with mild symptoms [1]

Core Viewpoint - The company has received approval from the National Medical Products Administration for two drug registration certificates for Carbidopa-Levodopa Extended-Release Tablets, enhancing its product pipeline in the Parkinson's disease treatment sector [1] Group 1: Product Approval - The Carbidopa-Levodopa Extended-Release Tablets (specification: Carbidopa 50mg, Levodopa 200mg) is the third approved product in the domestic market [1] - The Carbidopa-Levodopa Extended-Release Tablets (specification: Carbidopa 25mg, Levodopa 100mg) is the first generic version in the domestic market, with no original product registered for sale [1] Group 2: Market Opportunities - The approval of these products expands the company's opportunities in the Parkinson's disease treatment market [1] - The new products may lead to increased business prospects in this niche market [1] Group 3: Sales Uncertainty - The production and sales of the drugs may be influenced by changes in the market environment and other comprehensive factors, leading to certain uncertainties in sales performance [1]

公司卡左双多巴缓释片(规格：卡比多巴50mg、左旋多巴200mg)为国内第三家获批企业，卡左双多巴缓 释片(规格：卡比多巴25mg、左旋多巴100mg)则为国内首仿且该规格原研产品没有在国内进行注册销 售。 卡左双多巴缓释片的获批，丰富了公司在帕金森病治疗领域的产品管线，特别是其小规格产品成为国内 首仿，为公司在这一细分市场领域赢得了更多商机。卡左双多巴缓释片是左旋多巴与卡比多巴按4:1比 例组成的复方缓释制剂，被《中国帕金森病治疗指南(2020年版)》列为治疗帕金森病的"金标准"。公司 卡左双多巴缓释片的成功获批，为帕金森病患者提供了比较好的原研替代产品，其中小规格的获批，为 轻症患者的服药带来了便利性。 智通财经APP讯，精华制药(002349.SZ)发布公告，近日，公司收到国家药品监督管理局核准签发的卡左 双多巴缓释片的两个《药品注册证书》。 ...

Group 1 - Nearly 10 million people globally suffer from Parkinson's disease, a neurodegenerative disorder characterized by the gradual death of dopamine-producing cells in the brain, leading to symptoms such as tremors, muscle stiffness, slowed movements, and balance issues [1] - Each Parkinson's patient incurs approximately $10,000 annually in direct and indirect medical costs for treatment, which remains limited and lacks a cure [2] - The scientific community has been exploring the causes of Parkinson's disease for decades, aiming to improve symptoms and potentially predict onset, with some experimental therapies showing promise in reversing symptoms [3] Group 2 - According to predictions from the British Medical Journal, the number of global Parkinson's cases could exceed 25 million by 2050, representing a 112% increase from 2021 [4] - Research led by Professor Kay Double from the University of Sydney has identified a mutated protein, SOD1, in Parkinson's patients that loses its protective function and accumulates in the brain, causing neuronal damage [5][6] - A drug named CuATSM, designed to deliver copper directly to brain tissue, is being evaluated for its efficacy in potentially reversing Parkinson's symptoms by restoring the function of the SOD1 protein [6][7] Group 3 - In a two-phase experiment, the first phase determined the optimal dosage of CuATSM, with a dosage of 15 mg per kg of body weight found to effectively increase copper levels in the brain [7] - The second phase involved genetically modified mice with Parkinson's-like symptoms, where those treated with CuATSM showed no decline in motor skills, while the placebo group did, indicating a restoration of SOD1 function and protection of dopamine neurons [8][10] - The black substance in the brain is crucial for motor control, coordination, learning, and certain cognitive functions [9] Group 4 - Research from Stanford University suggests that inhibiting the overactive LRRK2 enzyme, associated with a genetic mutation in some Parkinson's patients, may stabilize the condition, particularly in early-stage patients [11] - Approximately 25% of Parkinson's cases are attributed to genetic factors, with LRRK2 mutations being the most common [11] - Initial experiments with a compound called MLi-2 aimed at reducing LRRK2 enzyme activity did not show significant changes, but extending the treatment period to three months resulted in restored communication between dopamine neurons and the striatum [12][14] Group 5 - The restoration of primary cilia in neurons and glial cells in genetically modified mice indicated potential for repairing damaged neural circuits in Parkinson's disease [14] - The MLi-2 therapy shows great potential in repairing Parkinson's-related neural circuit activity, with ongoing clinical trials for LRRK2 inhibitors expected to translate findings from mice to human applications [14][15] - Identifying early symptoms of Parkinson's is crucial for maximizing the effectiveness of the therapy, as symptoms may appear up to fifteen years before characteristic tremors [14]

Summary of Supernus Pharmaceuticals (SUPN) Conference Call Company Overview - Supernus Pharmaceuticals is a CNS-focused biopharmaceutical company with approximately eight products on the market, including legacy products and significant growth drivers [3][4] - The company reported profitable revenues around $600 million, despite the loss of exclusivity on flagship products [5] Key Products and Financials - **KELBRII**: A novel ADHD treatment launched in May 2021, currently generating a run rate of approximately $260 million. The product has significant growth potential with a large market of 100 million prescriptions annually [4][7][8] - **ONAPCO**: A recently launched infusion device for Parkinson's, with over 200 prescribers and 500 patient enrollment forms submitted within a month of launch. The peak sales potential is estimated between $200 million to $300 million [27][31][34] - Revenue expectations for 2025 are projected between $600 million and $630 million, with 2025 potentially being a trough year due to the full-year impact of generic competition for Oxtellar XR [6][7] Growth Drivers - The growth of KELBRII, GOCOVRI, and ONAPCO are expected to offset revenue losses from other products [6] - The company anticipates continued volume growth in prescriptions, with a historical growth rate of over 20% for KELBRII [10][11] Market Dynamics and Competition - The ADHD market is characterized by competition, but the company believes that competition can be beneficial for market growth [25][26] - Potential competitors for KELBRII include Osuka and Axsome, but the company remains optimistic about its long-term growth trajectory [22][23] Pipeline Developments - **SPN-820**: A novel mTORC inhibitor for major depressive disorder (MDD) is set to enter a Phase 2b study, with hopes of demonstrating a clinically meaningful reduction in depression scores [42][49] - **SPN-817**: An acetylcholinesterase inhibitor for epilepsy, with Phase 2 data expected by the end of 2027. The drug shows promise in reducing seizures while potentially improving cognitive function [57][61] Business Development Strategy - The company is actively pursuing business development opportunities, focusing on commercial assets and products that can be launched between 2026 and 2030 [68][69] - Supernus has a clean balance sheet with zero debt, providing financial flexibility for potential acquisitions [69] Conclusion - Supernus Pharmaceuticals is positioned for growth with a strong product portfolio and pipeline, despite facing challenges from generic competition and market dynamics. The company is committed to exploring business development opportunities to enhance its product offerings and maintain its competitive edge in the CNS market [70]